Recent studies have shown that chemotherapy destabilizes the blood vasculature and increases circulating tumor cell (CTC) influx into the circulation of metastatic cancer patients (Met-pa). CTCs are a precursor of cancer metastasis, in which they can migrate as single CTCs or as CTC clusters with stromal cells such as cancer-associated fibroblasts (CAFs) as cell aggregates. Blood samples were collected from 52 Met-pa, and the number of CTC and CAF was determined along with the temporal fluctuation of these through the chemotherapy treatment. In this study, CTC level was found to increase two-fold from the initial level after 1 cycle of chemotherapy and returned to baseline after 2 cycles of chemotherapy. Importantly, we determined for the first time that circulating CAF levels correlate with worse prognosis and a lower probability of survival in Met-pa. Based on the CTC release induced by chemotherapy, we evaluated the efficacy of our previously developed cancer immunotherapy to eradicate CTCs from Met-pa blood using an ex vivo approach and demonstrate this could kill over 60% of CTCs. Collectively, we found that CAF levels in Met-pa serve as a predictive biomarker for cancer prognosis. Additionally, we demonstrate the efficacy of our therapy to kill primary CTCs for a range of cancer types, supporting its potential use as an anti-metastasis therapy in the clinical setting.

中文翻译：

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在转移性癌症患者中，癌症诱导的成纤维细胞在集体迁移单位中由化学疗法诱导的循环肿瘤细胞释放到血液中。

最近的研究表明，化学疗法会破坏血管系统的稳定性，并增加循环肿瘤细胞（CTC）流入转移性癌症患者（Met-pa）的循环。CTC是癌症转移的前体，在其中它们可以作为单个CTC迁移，也可以作为CTC簇与基质细胞（如癌症相关的成纤维细胞（CAF））作为细胞聚集体迁移。从52 Met-pa采集血样，并通过化学疗法确定CTC和CAF的数量以及它们的时间波动。在这项研究中，发现1周期化疗后CTC水平比初始水平增加了两倍，并在2周期化疗后恢复了基线。重要的，我们首次确定循环CAF水平与Met-pa的预后较差和生存率较低相关。基于化学疗法诱导的四氯化碳释放，我们评估了我们先前开发的癌症免疫疗法使用离体方法从Met-pa血液中清除四氯化碳的功效，并证明这可以杀死60％以上的四氯化碳。总体而言，我们发现Met-pa中的CAF水平可作为癌症预后的预测生物标志物。此外，我们证明了该疗法可杀死多种癌症类型的原发性CTC的功效，支持其在临床环境中作为抗转移疗法的潜在用途。我们使用离体方法评估了我们先前开发的癌症免疫疗法从Met-pa血液中消除CTC的功效，并证明这可以杀死60％以上的CTC。总体而言，我们发现Met-pa中的CAF水平可作为癌症预后的预测生物标志物。此外，我们证明了该疗法可杀死多种癌症类型的原发性CTC的功效，支持其在临床环境中作为抗转移疗法的潜在用途。我们使用离体方法评估了我们先前开发的癌症免疫疗法从Met-pa血液中消除CTC的功效，并证明这可以杀死60％以上的CTC。总体而言，我们发现Met-pa中的CAF水平可作为癌症预后的预测生物标志物。此外，我们证明了该疗法可杀死多种癌症类型的原发性CTC的功效，支持其在临床环境中作为抗转移疗法的潜在用途。